Deck 2 Flashcards
1
Q
What is the association between NAFLD and AIH?
A
up to one third of patients with AIH have NAFLD, and concurrent NAFLD may influence response to therapy
2
Q
Can AZA or MMF be continued throughout pregnancy?
A
AZA can be continued in pregnancy
MMF needs to be stopped
3
Q
When can you attempt drug withdrawal in AIH?
A
Has to have at least two years of biochemical remission
Liver biopsy is preferred but not mandatory in adults, is mandatory in children
4
Q
What are second line agents in treatment for AIH?
A
MMF
TAC
5
Q
Do steroids need to be continued post transplant for AIH?
A
No, steroids can be discontinued after LT
6
Q
What ethnic groups and ages does AIH occur in?
A
AIH occurs in all ages and within all ethnic groups (vs PBC is an adult disease)
Alaskan Natives have icteric IAH
Hispanics more commonly have cirrhosis
AA have accelerated progression of disease and a higher recurrence after LT
7
Q
What are the genetic predispositions with AIH?
A
Involves HLA. There are non HLA foci, but these are less common
8
Q
What antibodies are found in type 1 AIH?
A
ANA
Smooth Muscle
9
Q
What antibodies are seen in Type 2 AIH?
A
liver kidney microsome
10
Q
ANA is found in what diseases?
A
PSC AIH Hep C Chronic Hep B NAFLD ALD
11
Q
Antismooth muscle Ab is found in what diseases?
A
AIH
PSC
Hep C
ALD
12
Q
At what age does Type 1 AIH occur vs Type 2 AIH
A
Type 1 is an adult disease
Type 2 is a childhood disease
13
Q
Which type of AIH had elevated IgG and which has reduced IgA
A
Elevated IgG- Type 1 AIH
Low IgA- Type 2 AIH
14
Q
What type of AIH are extra hepatic manifestations of IBD and Rheumatic disease seen in?
A
Type 1 AIH
15
Q
What type of AIH is vitiligo and DM seen in?
A
Type 2
16
Q
Can remission be achieved in Type 1 or Type 2 AIH?
A
Type 1 AIH, remission is rare in Type 2 and long term IS is typically needed
17
Q
what are compatible histological findings in AIH?
A
- Interface hepatitis
- Centrilobular necrosis
- Emperipolesis (penetration of one cell into another intact cell, with both cells retaining viability)
- Hepatocyte rosettes
18
Q
What is seen in autoantibody negative hepatitis?
A
- Antibodies may be expressed later in the course of the disease
- SLA and atypical pANCA may be seen
- *SLA I the only ab seen in about 20% Of patients with AIH and is associated with more severe disease
19
Q
What is the most common concurrent autoimmune disease in type 1 AIH and type 2 AIH?
A
in Type 1: Autoimmune thyroiditis
in Type 2: Autoimmune thyroiditis, DM 1, autoimmune skin (vitiligo)
20
Q
What should patients with AIH be screened for?
A
Celiac disease (prevalence is higher in ppl with AIH than general population)
Thyroid disease
21
Q
What is the paris classification for AIH overlap with PBC?
A
Two of the following Three should be met for PBC:
- Alk Phos >2 ULN or GGT >5ULN
- AMA
- Florid bile duct lesions
AIH: two of three needed
- interface activity is mandatory
- ALT >5
- IgG >2 or presence of SMA
22
Q
What are overlap syndromes?
A
It is a clinical description, but a non validated pathologic entity.
- So may help predict non-response to conventional treatment
- can increase risk of treatment failure, death or need for OLT
23
Q
What are six drugs that have a definite association with AIH?
A
- Minocycline (tetracycline)- latency period of up to 12 months
- Nitrofurantoin- latency period of up to 12 months
- Infliximab
- Alpha-methyldopa
- Adalimumab
- Halothane
24
Q
How do you treat drug induced AIH?
A
- remove offending drug with monitoring of labs (usually takes 1 month)
- Hy’s law= if LFT’s >2ULN + bill >2 –> start steroids because risk of death or LT is 9-12%
- Start steroids if labs do not improve after stopping offending drug
- if labs flare after stopping steroids, underlying AIH is likely
25
When does transient elastography detect fibrosis accurately in AIH?
After at least six months of successful immunosuppressive therapy to reduce hepatic inflammation
26
What vaccines are ok in patients on IS?
Recombinant and inactive vaccines are ok
| Live vaccines are not ok
27
What are 7pre-screening things you should do for a patient on AIH prior to starting steroids?
1. Test for absent or near abssent TPMT activity prior to starting treatment with AZA
2. vaccinate for Hep A and B
3. Check screening for Hep B
4. Screen for osteoporosis at baseline and every 2-3 years of continuous steroid treatment
5. check vit d at baseline and annually
6. supplement with elemental calcium (1000-1200 mg daily) and via D (at least 400-800 IU daily) while on steroid therapy and supplemented as clinically indicated
7. assessment of metabolic syndrome
28
Someone with AIH and HBsAg- but HBcAb+ and starting steroids should do what?
Undergo periodic testing with HBsAg and HBV DNA to detect reactivation and the need for on demand antiviral therapy
29
What dose and duration of steroids can increase risk of reverse seroconversion?
Moderate (10-20 mg daily) to high (>20 mg daily) for >/= 4 weeks
*reverse seroconversion = appearance of HBsAg and HBV DNA in a previously HBsAg negative patient
30
Which AIH patients should be start on antiviral therapy for HBV prophylactically
patients with serological evidence of previous HBV infection who are treated with high dose steroids or other immune modulations (B cell depleting agents)
31
What pregnancy complications are seen in AIH?
Fetal and still birth
Antiphospholipid antibodies
Premature birth
no specific birth defects
32
When should women with AIH cirrhosis have varies screened during pregnancy?
Varices screening prior to conception or during second trimester(when mothers blood volume increase) and treated with band ligation (BB can't be used in pregnancy)
33
How to treat AIH?
1. Induction:
Steroids 20-40 mg/D or budesonide (9 mg daily)
Check TMPT, start AZA two weeks after (50-150 mg/d), check labs every 1-2 weeks
2. Assess response by 4-8 weeks
- if biochemical response, then taper predicted to 5-10 mg daily over next six months (or budesonide 3 mg daily), maintain AZA, check labs every 2-4 weeks
3. Once remission achieved, may attempt steroid withdrawal while continuing AZA, check labs every 3-4 months
4. Once prolonged remission (24 months), can consider IS withdrawal
** I think if doing budesonside, then do it with AZA
34
How to treat AIH with cirrhosis?
1. Induction: steroids 20-40 g/day do not use budesonide. After two weeks can add AZA 50-150 (after checking TMPT), but can only use in compensated cirrhosis, not decompensated, check labs every 1-2 weeks
2. Assess response in 4-8 weeks, taper predicted to 5-10 mg over six months, maintain AZA
3. Once biochemical remission achieved, withdraw steroids, maintain AZA, check labs 3-4 months
4. Once prolonged remission of 24 months, can consider withdrawing IS
35
How to treat acute severe AIH?
Defined as jaundice, INR 1.5-2, no encephalopathy, no known liver disease
1. Do not use budesonide
2. Do not use AZA
3. Use prednisone 60 mg/day or IV steroids, lab testing every 12-24 hours
4. Assess response by 1 week, and if biochemical response, causing reduce prednisone. Consider AZA once cholestatis is resolved but check TMPT first. If no response, reevaluate diagnosis, consider second line drugs, and initiate transplant evaluation. If HE develops, then tx eval
5. Once remission achieved, use lowest IS, do not withdraw IS
36
How to treat AIH with ALF?
LT eval directly. Wouldn't try IS --> would go straight to LT eval
37
What is the most important index of outcome in AIH treatment?
Rapidity of response to treatment
Labs should improve within 2 weeks
Biochemical remission within 6 months is associated with signficantly lower frequency of progression to cirrhosis or LT --> so adjustments in therapy may be justified to improve the speed of response
38
What is the biggest pre-disposing factor to relapse in AIH?
Duration and completeness of inactive disease prior to disease withdrawal
39
How to treat AIH relapse?
1. Induce with standard Prednisone and AZA regimen
- can reinstate the ORIGINAL treatment until biochemical remission
2. During steroid withdrawal, increase AZA up to 2 mg/kg daily
40
What are third line treatment options for AIH?
Anti TNF
| Anti CD 20 (rituximab)
41
What is the rate of relapse after LT for AIH?
AIH recurs in 8-12% of patients within first year of LT and 36-68% after 5 years
42
What are two prognostic models for PBC?
GLOBE- predicts transplant free survival
| UK PBC- predicts the risk of liver transplant or liver related death
43
What is the best predictor of survival in PBC?
Bilirubin level
44
How does PBC appear on histology?
Florid bile duct- focal lesions show intense inflammatory changes and necrosis around bile ducts
45
Does the degree of ALK Phos elevation in PBC correlate with severity?
In patients without cirrhosis, the degree of elevation of ALP is strongly related to the severity of ductopenia and biliary piecemeal necrosis
46
What antibodies are specific to PBC?
AMA
SP100
GP210
47
What are the diagnostic criteria for PBC?
ALP Elevation
present of AMA or other PBC specific ab (SP 100. GP210)
Histologic evidence of nonsuppartative destructive cholangitis and destruction of interlobular bile ducts, if biopsy was obtained (biopsy not needed for diagnosis)
48
What autoimmune conditions are seen in PBC?
Sjogren
CREST (calcinois, Raynoud, esophageal dysfunction, Sclerodacytyl, telangiectasia)
Scleroderma
Raynaud
49
Is jaundice seen in AIH or PBC?
AIH
| only seen in PBC in late stage liver disease
50
When is a liver biopsy indicated in PBC
- only when there are no ab detected (no AMA, Sp100, gp210, anti kelch like 12)
- when you need to rule out concomitant AIH (i.e ALT is >5ULN)
51
How is AMA negative PBC different than AMA positive PBC?
```
AMA negative PBC
-higher prevalence of SMA and ANA
- more extra hepatic autoimmune diseases
-worse QOL
Response to UDCA is the same
```
52
If someone with PBC has mild interface hepatitis and positive ANA, what is that called?
nothing- these are features of PBC. It is only AIH/PBC overlap if two of the following are met (PARIS):
- ALT>5ULN
- IgG>2 ULN
- Liver bx with moderate or severe interface hepatitis
53
What is OCA?
- Farsenoid X receptor agonist
- should be used in PBC in combination with URSO (only when inadequate response to UDCA after 1 year)
- should only be used in compensated cirrhosis
54
What dose of OCA should be used in PBC?
start with 5 mg qd, then after three months can be increased to 10 mg qd if liver chemistries remain abnormal and patient is tolerating
55
what is side effect of OCA?
pruritus
56
How do you manage UDCA if your patient also needs bile acid sequestrants?
Give UDCA one hour before of 4 hours after the bile acid sequestrate
57
When should biochemical response to UDCA be evaluated?
12 months after treatment initiation. At this point, second line therapy can be considered
58
Can fibrates be used in PBC?
it is off label, should not be used in decompensated cirrhosis
59
What is treatment for pruritus in PBC
First line is anion exchange resins- cholestyramine, colestipol and colesevelam
Dose of 4 mg to a max of 16 g/day
given 1 hour before other meds or four hours after other meds
they are positive charged resins that bind to negative charged resins like bile acids
60
What are second line therapies for pruritus in PBC?
After anion-exchange resin, can try:
1. Rifampicin 150 to 300 mg BID
2. Oral opiate antagonists like naltrexone 50 mg qd
3. Sertraline 75 to 100 mg
4. antihistamines (although may cause worsening of dry mouth in SICCA patients)
5. Phenobarbital- but can worsen fatigue since it is a sedative, bit d deficiency and gingival hyperplasia
61
How to treat SICCA symptoms in s PBC
```
Dry eyes:
- artificial tears
-pilocarpine or cevimeline
- cyclosporine ophthalmic emulsion
Dry mouth
- saliva substitutes
- pilocarpine or cevimeline
```
62
What will happen to PBC symptoms during pregnancy?
Estrogen promotes cholestasis so oral contraceptive and pregnancy will worsen pruritus
63
How do you screen for PBC?
Screen for female FDR starting at age 30. Start with check ALP. If elevated, then check AMA. Could be repeated every five years
64
What is the long term follow up for PBC patients?
1. Check labs every 3 months
2. At 12 months see if inadequate responser to UDCA
3. Thyroid status every year
4. Osteoporosis every two years depending on baseline density
5. Fat soluble vitamins annually if bile >2.0
6. EGD every 1-3 years if cirrhosis, VTE >17kPA
65
How do you treat osteoporosis in someone with varies?
IV bisphosphonates, should avoid oral bisphosponates
66
what is needed for diagnosis of PSC?
MRCP or ERCP
Biopsy is not needed in patients with typical cholangiographic findings. If they don't have cholangiographic findings, then can get biopsy
67
What is a dominant stricture?
Stenosis with a diameter <1.5mm in the CBD or <1mm in the hepatic duct
68
What should a dominant stricture raise concern for?
cholangiocarcinoma. This is because CCA commonly occurs as a stenotic ductal lesion in the perihilar region. But, most stenotic lesions are benign more than malignant. Differentiating between dominant stricture and CCA is difficult
69
What ERCP method is needed for PSC dominant strictures?
spincherotomy AND balloon dilation. sphincterotomy alone is not enough
Balloon dilatation has been
shown to be effective alone.It may be performed
periodically with or without stenting. However, biliary stenting has been shown to be associated with increasedcomplications when compared to endoscopic dilatation only and should be reserved for strictures that are refractory to dilatation
70
What to do when unable to endoscopically reach dominant stricture?
can try percutaneous cholangiography with or without stunting
71
How often should you screen for osteoporosis in PSC?
at diagnosis and then every 2-3 years (pending results)
72
What should everyone with PSC get at time of diagnosis?
colonoscopy with biopsies. Because there can be rectal sparing and at higher risk of right sided Colorectal cancer, a full colonoscopy is needed.
If there is IBD and PSC, then surveillance colonoscopy with biopsies at 1 year to 2 year intervals from the time of diagnosis of PSC to exclude cancer
If initial colonoscopy is negative for IBD, should get colonoscopy every 3 to 5 years
73
What does the UC colitis in PSC typically look like?
Usually more extensive, but tends to run a more quiescent course
Pancolitis
Rectal sparing
Backwash ileitis
74
Patients with colectomy and PSC are more prone to what?
pouchitis if they have an IPAA
75
What happens in patients with PSC with ileostomy?
more prone to develop peristome varies, if they develop portal hypertension. Can be controlled with TIPS or liver transplant. IPAA is less complicated with vatical formation
76
When do you need to do a cholecystectomy in patients with PSC?
In patients with PSC + gallbladder mass lesions, regardless of lesion size (because risk of cancer is so high)
77
How frequently should gallbladder be assessed in PSC?
annual ultrasound to detect mass lesions (remember, lesion of any size on gallbladder --> cholecystectomy)
78
What are causes of second sclerosing cholangitis?
1. Cholangiocarcionma
2. choledocholithiasis
3. Diffuse intrahepatic metastasis
4. Eosinophilic cholangitis
5. Histiocytosis
6. IgG4 associated cholangitis
7. Intra-arterial chemotherapy
8. Ischmiec cholangitis
9. mast cell cholangiopathy
10. portal hypertensive biliopathy
11. Recurrent pancreatitis
12. Recurrent pyogenic cholangitis
13. surgical biliary trauma
79
What should be given to patients with dominant strictures in PSC undergoing ERCP?
antibiotics- to effectively resolve cholangitis
80
What should be done in patients with recurrent and refractory cholangitis?
recurrent- prophylactic antibiotics
| refractory- liver transplant
81
What is a risk factor for IBD in patients with PSC?
duration of PSC
| * note duration of PSC is not a risk factor for cholangiocarcinoma
82
What are risk factors for cholangiocarcinoma in PSC?
| When is cholangiocarcinoma seen in PSC?
Risk factors:
1. Elevated bilirubin (so if someone with PSC deteriorates or has worsening labs, should eval for CCA)
2. Varcieal bleeding
3. Proctocolectomy
4. Chronic UC with dysplasia or cancer
5. Duration of IBD (but not duration of PSC)
6. Polymorphisms in NKG2D
It is usually seen at time of diagnosis or within the first year (which is why they don't think duration of PSC is a risk factor for CCA)
83
What can CA 19-9 tell you in PSC?
If >130, has high specificity for CCA. But CA 19-9 can be elevated in bacterial cholangitis too
84
How to make diagnosis of CCA?
Can use CA 19-9, MRI, ERCP with brushings for conventional cytology and FISH
85
When is liver transplant acceptable for CCA?
Early stage CCA:
| - unicentric mass lesions
86
What is PFIC 1 characterized by?
Gene?
Level of GGT?
Severe cholestasis during infancy, high levels of bile acids, soluble vitamin deficiency
ATP8B1
FIC1
GGT is normal
87
What is PFIC 2 characterized by?
GENE?
GGT?
- severe cholestasis of infancy, high levels of BA, pruritus (only thing different from PFIC 1 and in PFIC 1 see fat soluble vit deficiency
- most common
- ABCB11 and BSEP
- GGT is normal
88
What is PFIC 3 characterized by?
Gene?
GGT?
Neonatal cholestasis
Least common
ABCb4 and MDR3
GGT elevated
89
PFIC 4
Severe cholestasis during infancy
TJP2
GGT is normal
90
PFIC 5
Rapidly progressive
NRH1H4/FXR
GGT - ???
91
What is seen in Alagille syndrome?
It is autosomal dominant mutation JAG1 (90%) and NOTCH2
Pacity of bile ducts, pruritus, Pulm stenosis, butterfly vertebrae, triangular facies
Schwalbe line
92
BRIC disease
Gene mutation in ATP8B1/ FIC1 (same as PFIC 1), can present in adulthood
93
What gene is involved in HHT?
Mutation in endogeni-TGF beta signaling (ENG) or active reception like kinase type 1
94
How to make the diagnosis of HHT?
Requires three of the four:
1. epistaxsis
2. cutaneous or mucosal telangiectasia
3. Involvement of lung, CNS, GI tract, liver
4. Family history HHT
95
What are the liver manifestations of HHT?
Shunting/AVMs which lead to portal HTN and biliary ischemia --> followed by elevation of all phos and GGT
Normal synthetic function BUT imaging may show psedocirrhosis
Can also show NRH and FNH
96
What are the non hepatic involvement of HHT?
High output cardiac failure
| Cerebral AVM's
97
What is treatment of HHT?
aimed at anti-angiogenesis (bevaczimub)
| liver transplant is considered curative when there is liver involvement
98
What is needed to get meld exception for HHT?
Documentation of high output cardiac failure by echo
Imaging supporting intra-hepatic AVM's or severe diffuse bilobar necrosis in the setting of hepatic AV malformatio
99
What is the gene involved in Wilson disease?
ATP7B- absent or reduced, so decreased heaptocellular excretion of copper into bile --> leading to hepatic copper accumulation and injury
100
What levels of cerulplasmin are seen in Wilson?
Usually <20 (but not always). Ceruloplasmin without copper (apopcerulplasmin) is less stable that when ceruloplasmin is bound to copper. Because copper is stuck in the liver, it cannot be bound to ceruloplasmin and so due to instability of apoceruloplasmin, the {} is low
101
What can you expect to see in ALF from Wilson?
AST:ALT ratio >2.2
Alk phos t bili ratio <2
This is 100% specific for Wilson disease
102
What are renal, skeletal and cardiac symptoms of Wilson?
Renal -aminoaciduria and nephrolithiasis
Skeletal- premature osteoporosis and arthritis
Cardiomyopathy and dysthymias
103
What liver stain is helpful in Wilson?
Rhodamine stain- stains for copper
104
What are ocular symptoms of Wilson?
Kayser Felisher rings (but also seen in other cholestatic diseases)
Sunflower cataracts
105
What urine copper concentration is seen in Wilson?
Usually >40 is indicative of Wilson. Because it is not being absorbed in the blood stream, there is extra copper being utilized by other organs like the kidney
106
What are the three major components for Wilson diagnosis>
KF rings present
Ceruloplasmin <20
24 hour urine Copper >40
If all three are present --> diagnosis of WD established, and no biopsy is needed
107
What hepatic concentration of copper is diagnostic of Wilson?
250 mcg/dry weight
| if <40-50, almost always excluded Wilson
108
When is molecular testing needed for Wilson?
KF rings present
CPN>20
24 hour urine >40
Hepatic Cu { } <250
Or in other situations where KF rings are absent, but you have some other features concerning for Wilson
109
When is serum Ceruloplasmin helpful in Wilson?
extremely low level <5 mg/dL is strong evidence foe diagnosis of Wilson
Moderately subnormal evidence suggests further evaluation
But if ceruloplasmin is in normal range, this does not exclude diagnosis, because it can be an acute phase reactant
110
What is the Penicillamine challenge and which population is it most helpful in?wi
It is when you give Penicillamine at start of 24 hour urine collection and again at 12 hours. Give 500 mg (not weight based), and if urine concentration of copper is >1600/24 hours, then may be Wilsons.
Standardized in children, not so much in adults (because unreliable for excluding Wilson in asymptomatic siblings)
111
Pediatric patients with autoimmune hepatitis should be evaluated for what?
wilson disease
112
adult patients with atypical AIH or those who do not respond to steroids, should be considered for what?
Wilson
113
What can be seen on biopsy for Wilson?
steatosis, but generally not as severe as NAFLD
114
what is often seen in ALF from WD?
hemolytic anemia, coombs negative
modest elevation in ALT, AST, AST:ALT >2
low alk phos
alk phos:bili ratio <2
115
Who should be screened for Wilson?
First degree relatives
Can do molecular testing for ATPB7 or Haplotype testing
OR
Can do ceruloplasmin, urinary cu, aminotransferases, slit lamp
Should be done in patients starting at age three or older
116
What is treatment for Wilson?
Chelating agent (pencillamine or Trientine -trientene may be better tolerated)
Zinc - used for maintenance therapy, but some are using as first line therapy (urine Cu should be <75)
Symptomatic - chelating agent, avoid food high in {Cu}
Asymptomatic and maintenance therapy = chelating agent or zinc
Treatment is lifelong, unless liver transplant obtained
117
How does zinc work in Wilson?
induce enterocyte metallothionein, which has a greater affinity for Cu than for Zinc. So it binds to cu and inhibits entry into portal circulation, and you poop out zinc
118
How do you manage Wilson in pregnancy?
can still use chelating agents, but need to reduce dose
119
Patients on chelation therapy should have what checked?
CBC (neutropenia, thrombocytopenia)
U/A (proteinuria)
at least twice a year, no matter how long they have been on it
120
What is the expected urine Cu on chelation therapy for Wilson?
What about on zinc?
And how often should it be checked?
Urine Cu on chelation therapy is 200-500
Urine Cu on zinc should be <75
Checked at least once a year
121
Someone who is non adherent to chelation therapy, will have what levels of urine cu?
can have really high levels (also seen in the start of therapy)
can be really low urine Cu as well, but with high levels of non-ceruloplasmin bound copper (vs in over treatment can have low urine Cu but low non-ceruloplasmin bound copper)
122
Overtreatment with chelation therapy in Wilson, will show what urine Cu?
will have low urine cu with low non-ceruloplasmin bound Cooper
123
Liver failure from Wilson means what for transplant
status 1A
124
What is the pathophys of A1AT deficiency in liver disease and Pulm disease
A1AT is a protein that inhibits elastase. So by inhibiting elastase, elastase cannot eat up the lung.
In Pulm disease, it is loss of function, so there truly is no A1AT to inhibit elastase
In hepatic disease, there is A1AT, it is just misfolded, so it cannot leave the liver and accumulates. This only really happens in the ZZ phenotype or SZ in children. MZ is asymptomatic and over expressed in NAFLD
In Null disease (Pi Null Null), there will be lung disease, but no liver disease, because there is no A1AT accumulation, just a deficiency
125
How do you make a diagnosis of A1AT defiency
Level of A1AT
Phenotype (Z, S)
or SERPINA1 gene
126
What do you see on pathology for A1AT deficiency?
PAS Schiff stain in Endoplasmic reticulum (where A1AT is made)
127
What does A1AT cause in children
neonatal hepatitis syndrome
128
What is tx of A1AT?
```
smoking cessation
modifying risk factors for liver disease
avoid saids
refer to pulm
replacement therapy with AAT for lung disease but not indicated for liver disease
```
129
What mutation is seen in amyloid?
TTR or transthyretin gene mutation
130
How is diagnosis made of amyloid?
congo red stain of liver or other tissue
131
What is treatment for amyloid?
Liver transplant, TTR is made by the liver
Will often do a domino transplant, because the liver is otherwise functioning, and although it will continue making the TTR gene, it takes years to cause issues in other organ
Can get MELD exception points but needs to either have a good EF or also be listed for heart transplant
132
Type 1 choledochal cyst
CBD dilated
| Treatment is extra hepatic bile duct resection and Roux en Y HJ
133
Type 2 choledochal
Diverticulum, extra hepatic
Tx is simple excision
low risk of malignant transformation
134
Type 3 choledhochal cyst
choledochocele, so cyst in duodenum
Tx is endoscopic sphincterotomy
low risk for malignant transformation
135
Type 4 choledocal cyst
both intra and extra hepatic cyst in type A
just extra hepatic in type B
Tx: hepatectomy in type A
and extra hepatic bile duct excision in type B
136
Type V cholecocal cyst
just intrahepatic
Caroli, congenita hepatic fibrosis
PCKD
Tx: liver reaction or transplant
137
What are the MELD exception requirements for Cystic Fibrosis?
1. FEV1<40% within 30 days of exception request
Adults get MMAT-3
12-17 years old get MMAT
<12 years old get MPAT
138
What is erythropoietic protoporyhia
deficiency in ferrochetalase that catalyzes formation of heme from protoporhyrin and iron
excessive production of protoporhyin in bone marrow
increased biliary excretion-toxic to biliary epithelium and biliary fibrosis
photosensitivity, abdominal and back pain
liver transplants treats cirrhosis, but EPP liver disease may recur (because its a problem in the bone marrow)
Must place filters in OR to absorb wavelengths that excite protoporphyrin that can cause tissue injury
X- linked--> males
139
Mitochondrial DNA mutations cause what
myopathy and encephalopathies
140
Which patients should be evaluated for hemochromatosis?
all patients with evidence of liver disease
141
How do you diagnose HH?
in symptomatic and asymptomatic patients, you start with a transferrin saturation and ferritin. If TS is >/= 45% OR ferritin is elevated, then get HFE genotyping
If you are a 1st degree relative of someone with HH, go straight to HFE genotyping. This is to detect early disease and prevent complications
142
When is a liver biopsy indicated in HH?
Three scenarios:
1. when there is phenotypic markers of iron overload but are not C282Y homozygotes
2. non HFE related HH
3. Stage the degree of liver disease in C282Y homozygotes if liver enzymes are elevated OR if ferritin >1000
143
What ratio of hepatic iron index is helpful in HH?
>1.9 means HH, not secondary iron overload
measures the rate of hepatic iron growth (dividing the HIC/age) which thought that someone with HH will continue to absorb iron, whereas someone with secondary iron overload or heterozygosity will not
144
What are target levels of phlebotomy in HH?
Target levels should be ferritin level of 50-100 in patients undergoing phlebotomy
145
What dietary changes are needed during phlebotomy for HH?
none, but don't take vitamin c and iron supplements
146
Do you need to have cirrhosis from HH to start phlebotomy?
No- initiation of phlebotomy before the development of cirrhosis and/or diabetes will reduce Morbidity and mortality of HH
147
Which symptoms are ameliorated by phlebotomy in HH?
malaise, fatigue
skin pigmentation
insulin requirements (note, diabetes won't go away completely)
abdominal pain
148
which symptoms are not fixed by phlebotomy?
arthritis
hypogonadism
advanced cirrhosis
diabetes
149
When should iron chelation be used?
secondary iron overload with dyserythropoietic syndromes or chronic hemolytic anemia. can use deferoxamine or deferasirox
150
What is pathophys of HH?
ferroportin- transports iron from cell to blood
hepcidin- blocks ferroportin
C282Y mutation --> hepcidin deficiency (so nothing to block ferroportin and tons of iron gets out of enterocyte; *** normally hepcidin blocks ferroportin)
?
1. causes decrease in hepcidin (Which normally inhibits iron absorption)
2. without hepcidin, iron levels increase --> hepcidin increases and breaks down ferroportin --> no ferroportin, no way for iron to get out of enterocyte
151
What is seen in type 2 HH
```
hemojuvelin or hepcidin
cardiomyopathy, hypogonadism
CONGENTIAL HEPATIC FIBROSIS
autosomal recessive (as is type 1)
occurs earlier onset (<30 years)
```
152
What is seen in Type 4 HH?
```
ferroportin disease
AUTOSOMAL DOMINANT
IRON IN KUPFER CELL AND HEPATOCYTES
lots of iron in spleen
lower tolerance to phlebotomy and may have anemia
```
153
What is life expectancy in HH?
normal life expectancy if treated before cirrhosis
154
Which hepatitis are DNA and which are RNA?
Hep B is only DNA
155
Which hepatitis are fecal oral vs which are parenteral? Which are sexual?
Hep A and E are fecal oral (the ones that have only acute phases are fecal oral). But at risk are MSM, IVDU, homeless, contaminated food
Hep B, C, D are parenteral
Hep B, D are sexual, c can also be sexual in some cases
156
Which can cause fulminant hepatitis and which can cause chronic hepatitis (and what is definition of chronic hep)
Fulminant: B, D, Can happen with A, C, E but rare
Chronic: B, C, D. Not in A or E - elevated labs and or viral markers for > 6 months
157
What is the clinical presentation of acute viral hepatitis?
usually starts with a prodrome of fever, malaise, low grade fever, RUQ pain - last for about a week
Then can be either icteric (pruritus, dark urine, prodrome usually gets better by this point) or non icteric phase - last for 7-28 days
Then generally self resolves
158
Who should be vaccinated against Hep A before exposure?
- anyone with chronic liver disease
| - anyone undergoing solid organ transplantation-
159
Can Hep A cause liver failure?
yes, but very rare. If it occurs, prognosis is poor
160
Who should be screened for Hep B? And how?
Screen those at risk
- people born in countries with a high prevalence (Asia, Africa, pacific islands)
- us born patients who were not vaccinated as infants and whose parents were born in endemic regions
- HIV positive
- IVDU
- MSM
- household contacts or sexual partners of ppl with HBV
- pregnancy
- those needing IS
Screen with HBsAg and anti-HBs. Do not need to routinely use anti-HBc for screening unless HIV infection about to undergo HCV or anti cancer and other IS or renal dialysis
161
What to do if a HCW has HbsAg+
only those whose job requires exposure prone procedures are talk to their institution. They should not perform exposure prone procedures if HBV DNA >1000. If <1000, can do procedures
162
If you have positive anti-HBc only, should you be vaccinated?
depends on risk factor. if no risk factors and NOT from endemic area, then yes, should be vaccinated.
If risk factors or from endemic area, then should not be vaccinate
163
Can pregnant women receive Hep B vaccination?
yes, it is safe. and if unvaccinated, should get it
164
What threshold in pregnancy requires Hep B treatment?
1. all standard indications
2. if doesn't meet standard indication, but DNA >200,000 in the second trimester (week 26 and 28), should be treated to prevent mother to child transmission, even if ALT is normal, can start TDF between week 28 to 32 (want to start on earlier side to allow time for VL to decline)
165
Can women with Hep B breastfeed?
yes!
166
What vaccinations are available for Hep B?
Three dose: 0,1,6 months
Twinrx: 0,7,21-30 days and 12 months (4 doses) with A
Two dose: Heplisav at 0 and 1 month
For non responders, a repeat three dose vaccination is recommendaed with a double dose used for immunocompromised patients, including those with cirrhosis
167
What imaging is ok in pregnancy and breastfeeding?
U/S- ok in pregnancy and breastfeeding
MRI without contrast ok in pregnancy and breastfeeding
MRI/MRCP with contrast- not ok in pregnancy, breastfeeding is safe after getting gadolinium (Gadolinum is contraindicated)
CT scan without contrast Yes (if MRI insufficient), yes in breastfeeding
CT scan with contrast- yes in pregnancy (second trimester when organs have formed) and ok to breastfeed after getting contrast. Should use low radiation, less than 50mGy
168
How often do you need to monitor mom's with normal ALT but HBV DNA >200,000 in second trimester?
- -Start TDF at week 28-32
- --can stop T-DF after delivery or up to 3 months post party
- -Will need to monitor ALT and HBV DNA every three months through 6 months post partum (risk of flare after stopping antivirals)
169
Which Hep B drugs are safe in pregnancy?
- Initiate or transition to TDF during Pregnancy.
- Others are not safe or lower barrier to resistance
- ok to breastfeed while on TDF
170
When is the highest MTCT risk for Hep B?
During delivery- risk of vaginal vs c section is the same
Some risk if undergoing amnio
No increased risk with breastfeeding
171
when is risk of AIH flares the highest?
| What are risk factors for flares?
flares can occur anytime during pregnancy, but immune system revs up towards the third trimester, so most common to get it during first three months after delivery.
Risk factors for flares include
- no AIH treatment in pregnancy
- shorter remission before conception (<1 year)
172
What factor predicts maternal risks in those with cirrhosis?
pre pregnancy MELD
if <6: no complication
>10, higher complications
173
When is the risk of variceal bleeding the highest?
second trimester due to intravascular volume expansion and enlarging uterus compressing the IVC
Note: mode of delivery is guided by obstetric indications, not presence of cirrhosis
174
When is variceal screening needed in pregnancy?
depends on if they had variceal screening within 1 year prior to conception.
If they did have EGD within 1 year:
- no varices --> no treatment
- small varices: consider NSBB
- Medium or large varices: NSBB or EVL until obliteration
If they did not have EGD within 1 year:
- do EGD
- if small varices: NSBB
if medium to large: NSBB vs EVL
175
How high can LFT's be in hyperemesis gravid arum?
up to 1000's, self resolves, first trimester usually
176
When does AFLP typically occur?
| What are risk factors?
Usually during third trimester through early postpartum period
low maternal BMI, Male fetus, multiple gestations (i.e twins), first pregnancy
177
What is pathophys of AFLP?
homozygous long chain 3 hydoxyacyl co-A hydrogenase (LCHAD) deficient offspring --> spill unmetabolized LC fatty acids in maternal circulation --> cause micro vesicular steatosis
178
What is the most common pregnancy specific liver condition? When does it occur? What are risk factors?
ICP
second to third trimester
Risk factors: HCV, advanced maternal age, metabolic syndrome, cholestatic mutations (ABCB11, ATP8B1)
179
What is diagnosis and treatment of ICP
Bile acids ?10
UDCA lowers bile acid levels and improves fetal outcomes (fetal risks = preterm birth, IU fetal demise, neonatal respiratory depression)
180
When can you get pregnant post transplant>
- as soon as a few weeks after transplant. so important to counsel
- try delaying 1 year post transplant to help ensure graft stability and lower IS
181
Which pregnant population should be screening with HbsAg?
all pregnant patients!
182
Which pregnant patients should be test for HCV? and if positive, when should they be started on treatment?
all pregnant patients! if positive, should be started on treatment after pregnancy and after breastfeeding (no data on DAA during breastfeeding)
183
How long to wait until pregnancy if on ribavirin?
Men or women who are on ribavirin (teratogenic) should be on contraception. Conception should be deferred for at least six months following last ribavirin use
184
What procedures should be reduced to limit MTCT transmission in HCV?
prolonged rupture of membranes
invasive fetal monitoring
episiotomies
all these should be avoided
185
What are pregnancy consideration in Wilson?
1. zinc is safe in pregnancy and conception should wait until on zinc monotherapy
2. chelating agents dose needs to be reduced in second and third trimester, should be increase post delivery
3. breast feeding is not recommended as all WD drugs are excreted in breast milk and risk of Cu deficiency in infant
186
What should reproductive age women with NAFLD be screened for?
polycystic ovary syndrome
187
Is breastfeeding good in NAFLD?
yes! longer duration is associated with lower rates of future NAFLD among offspring and reduced maternal metabolic complications
188
How does one manage hepatocellular adenomas in pregnancy?
- monitor hepatocellular adenoma each trimester with U/S and up to three months post partum
- if less than 5cm, pregnancy is not contraindicated
- if greater than 5 cm, prophylactic tx with embolization or resection should be considered prior to conception to minimize risk of rupture
189
How to manage hepatic hemangioma during pregnancy?
regardless of size, no monitoring required
190
How do you manage FNH in pregnancy?
no monitoring, regardless of size
191
What vitamin deficiency should be monitored pregnancy in PBC and PSC?
Vit K deficiency should be corrected, and regular monitoring of PT is recommended
192
What anticoagulation is ok in pregnancy and breastfeeding?
low molecular weight heparin
| Vit K antagonists are contraindicated during pregnancy, but ok during breastfeeding
193
Which sedation is safe in pregnancy?
meperidine
midazolam
propofol
fentanyl
194
In someone with HELLP- presents with abdominal pain, shoulder pain, or hypotension, then what?
get U/S to look for hemorrhage/hepatic rupture
195
What should be done in all patients with AFLP?
U/S to rule out hepatic infarct, hemorrhage
196
What screening is needed in newborns in mothers with AFLP?
deficiency of LCHAD
197
Is tacro safe in pregnancy?>
yes
198
What is management of acute hep B?
- no treatment since most cases will resolve
- will need treatment if progressing into ALF
- need to check HBsAg and ALT three to six months later to see if resolved or progressed to chronic hepatitis
199
Someone with Hep B core Ab but HBsAg-, can they transmit?
no
200
When does someone with Hep B Core Ab require vaccination
If Hep B core Ab +, HbsAg-,
vaccinate if from low endemic area and no risk factors
if from endemic area or if risk factors, should not be vaccinated unless has HIV or are immunocompromised
201
What to do if HbeAg+, DNA >20,000, ALT <2ULN?
get a biopsy or elastrography. If significant inflammation or fibrosis, should treat
202
What to do if HbeAg -, DNA>2000, ALT <2ULN
biopsy or elastrography. if inflammation or fibrosis --> treat
203
What are high risk populations for HCC in Hep B?
* anyone with HbsAg+ should be screened for HCC
1. HbsAg+ black or asian men >40, asian women>50
2. first degree family member with HCC
3. HDV
204
in HBV/HCV co-infection, how do you determine who gets what treated?
1. All HCV should be treated
2. Determination of Hep B treatment is the same as Hep B treatment mono
3. If not being treated for Hep B, and started on DAA, Hep B DNA and ALT should be monitored closely as this can cause a flare
205
What should be tested in anyone undergoing IS?
HbsAg and anti Hbc
HbsAg + and antiHbc+ --> should be treated prior to IS
206
What to do if HbsAg- and antiHbc+ and undergoing IS?
can monitor
but will have to treat if getting Cd20 or stem cell transplant
once prophylactic started, should be continued for 6 months AFTER therapy completed or 12 months after therapy completed if cd20
207
HbsAg+ undergonig liver transplant
prophylactic needed with NA with or without HBIG
low risk- short term HBIG or no HBIG
high risk- long term HBIG (HDV, HIV, non adherent)
208
HbsAg- recipient
| HbsAg- but antiHbc+ graft
long term antiviral therapy, lifelong
209
HbsAg-, antiHBc + non liver recipients who are getting a non liver organ
need close monitoring, alternatively can treat for first six months of transplant when IS ishighest
210
HBsAg- antiHBc + non liver recipient
| get antiHBc + non liver organ
monitor, no treatment
211
What is immune active CHB
ALT >2ULN or evidence of histologic disease
PLUS
elevated HBV DNA above 2000 in HBeAg - or above 20,000 in HBeAg+
always requires treatment
212
What if immune active but ALT<2ULN or DNA not high enough (20,000 or 2000)
treat if >40 years old, family history of cirrhosis or HCC, previous treatment
213
What drug to avoid if previous history of lamuviduine resistance?
avoid entecavir
214
What to do if:
| - HBeAg + without cirrhosis but with CHB who serovoncert to anti-He while on therapy?
treat for 12 months of persistently normal ALT. Then can stop treatment and monitor closely for one year
* note if same scenario, but with cirrhosis, then should treat indefinitely even if they seroconvert due to risk of decompensation
215
What type of cirrhosis and Hep B do you treat?
all, doesn't matter DNA, ALT, or compensated, decompensated
should treat all
Entecavir and TDF in decompensated cirrhosis. TAF not studied in decompensated patients, but can be considered if bone or renal disease. Can't use PEG in decompensated cirrhosis
216
Who should be screened for HCV?
all pregnancy patients
| all adults 18-79
217
What are risk factors for Hep D?
```
High risk sexual behavior
IVDU
MSM
Needle stick
Household contacts
dialysis
```
218
What percentage of Hep B patients are co-infected with Hep D
about 5-13%
219
What liver complications are seen with Hep D
can be acute or severe
| associated with accelerated course of fibrosis, HCC, early decompensation
220
How does the Hep B viral load affect Hep D
Hep B viral load has no impact on HDV viral load or outcomes.
Most common for Hep B replication to be suppressed, and predominantly Hep D replication
221
How are outcomes different for confection vs superinfection with Hep D
With co-infection --> more likely to have spontaneous clearance of Hep B
With superinfection (get Hep D after being infection with Hep B), then unlikely to have sponatanous clearance, and more likely to develop chronic hepatitis
222
Who should be screened for Hep D
HBsAg+ patients with HDV risk factors
Low HBV DNA but high ALT
test with anti-HDV and HDV RNA
223
Is a biosy helpful for BA
will show biliary obstruction but not diagnostic
224
What do you see in HIDA scan in BA
taken up into liver, but not excreted
225
what do you expect to see in IOC cholangiogram in BA
they stick the gallbladder (so must have gallbladder) and inject dye. Dye should do two things:
1. go into intestine via common bile duct
2. go up into liver (in some forms of BA, Common hepatic duct is atretic and won't go into liver)
226
What are the main causes of ALF in neonates vs kids 3-18
1. indeterminate
2 tylenol
3. AIH
For neonates:
1. indeterminate
2. Metabolic
3, viral
227
What is seen in GALD and what is treatment
baby in ALF, no splenomegaly (because patent venous) but with portal hypertension (ascites) and REALLY HIGH AFP
also with high iron in all tissues not just liver --> salviary biopsy with lots of iron (remember GALAD is also Hereditary hemochromatosis)
treatment: IVIG and excahgne transfusion (in second and third trimester, mother immunoglobulins pass the placenta and start attacking baby liver, so after birth can give IVIG to neutralize immunoglobulins and exchange transfusion to remove immunoglobulins)
228
what is seen in mitochondrial hepatopathy
ratio of lactate pyruvateratio, high CK
229
what is seen in tyrosinemia
high AFP and high urine succinyclacetone
230
What is seen in HLH
two cell lines down in CBC
high ferritin
high fasting triglycerides
high IL2R
low NK cell activity
231
kid with ALF and on vaproic acid
may have a mitochondiral depletion syndrome POLG1 mutation
232
when to use NAC in peds ALF
only if tylenol alf, if non tylenol ALF, actually worse outcomes if use NAC
